The overall aim of these studies is to increase our understanding of the neural mechanisms involved in mediating the perception of pain. The specific aim of the proposed studies over the next 3 years is to extend our successful studies initiated during the current granting period on (1) the function of the pathway ascending from subnucleus caudalis (SNC) of the brainstem trigeminal (V) nucleus to ventrolateral orbital cortex (VLO) via a relay in nucleus submedius (Sm) in medial thalamus and (2) the characteristics of neurons in the V system activated by sensory stimulation of cerebral blood vessels. Recent anatomical studies have described a pathway originating in the marginal layer of SNC. relaying in Sm and terminating in VLO. Indirect evidence strongly suggests that this pathway is involved specifically in the processing and relay of pain signals. No physiological studies apart from our own have addressed this potentially very important pathway. In addition, virtually nothing is known concerning the sensory receptors associated with the cranial blood vessels. These V afferents are believed to mediate vascular head pains such as migraine and thus it is of scientific and clinical importance to determine their physiological properties. The studies will be carried out in anesthetized rats and cats and employ primarily single cell electrophysiological recording techniques. The studies will characterize the functional properties of neurons in SNC that project to Sm, as well as neurons in Sm and VLO. Other experiments will be devoted to investigating in greater detail the types of peripheral stimuli and chemical agents which activate and influence the sensitivity of the sensory afferents innervating the cerebral vasculature. Some of these latter studies will be conducted in the rat where in addition to recordings from SNC neurons, recordings will be obtained from V ganglion neurons in order to determine the functional characteristics of the sensory fibers innervating the intracerebral vessels. The findings of these various experiments will help provide a clearer explanation of the processes underlying the perception of acute and chronic pain and will help explain the etiology of vascular headaches. In addition, the results may lead to the development of improved clinical methods for the control of pain.